In spite of being perceived as a disease of the past, syphilis remains a serious global health problem, affecting millions worldwide in both developing and developed countries. In underprivileged setting, syphilis is a significant cause of stillbirth and neonatal mortality due to vertical transmission during pregnancy, while in developed countries, it affects particularly high risk groups such as men who have sex with men (MSM). If untreated, syphilis often results in serious neurological and cardiovascular complications, including blindness, deafness, stroke and aortic aneurism. A better and simpler diagnostic test is desired to replace the current two-assay diagnostic tests, especially if early diagnosis and disease staging can be distinguished. A practical proteome-scale platform for antibody profiling has never before been available to the syphilis research community, and this technology has the power to rapidly discovery novel biomarkers and improve syphilis diagnostics approaches. Antigen Discovery, Inc. (ADI) of Irvine, CA, will develop a Treponema pallidum subspecies pallidum (TP) panproteome microarray to measure specific anti-TP IgG and IgM antibody levels in longitudinally collected sera from rabbits experimentally infected with syphilis agents and in patient sera. To this end, ADI will partner with two established syphilis investigators, Dr. Lorenzo Giacani, based at the University of Washington and expert in the use of the rabbit model of syphilis, and Dr. Jeffrey Klausner, based at UCLA, renowned for his syphilis epidemiological studies in MSM and transgender women in Lima, Peru.The panproteome array will include up to 1,000 syphilis proteins representing two groups of modern syphilis strains currently circulating globally. We hypothesize that certain anti-TP antibodies can serve as biomarkers to detect early infections or repeat infections, as well as different disease stages. The most promising diagnostic candidates will be identified in the rabbit model, which has exquisite control over the timing of sample collection after infection, treatment and reinfection. Subsequently, the top candidates will be confirmed in humans by testing the sera from Peruvian patients with varying stages of disease. We expect to identify several TP proteins that are recognized by antibodies, some which appear soon after infection and some that correlate with the stage of disease. Future studies will validate diagnostic markers and develop a prototype diagnostic test that can be tested for FDA 510(k) clearance. This application addresses the necessity of simplifying and improving syphilis diagnostics approaches, and choses to do it through the application of an innovative proteomic technology mastered by ADI. If successful, our endeavor will provide new tools and knowledge to help stem the spread of this serious infection.